1874
V. O. Iaroshenko et al.
PAPER
Colorless solid; yield: 0.28 g (54%); mp 279–280 °C (i-PrOH).
Colorless oil; yield: 0.32 g (84%); mp 127–128 °C; Rf = 0.80
(EtOAc).
1H NMR (DMSO-d6): d = 7.71 (s, 1 H, CH), 8.11 (s, 1 H, CH), 12.07
(s, 1 H, NH).
1H NMR (DMSO-d6): d = 2.63–2.71 (br s, 2 H, CH), 1.94–2.00 (m,
1 H, CH), 2.25 (m, 1 H, CH), 3.40–3.51 (m, 2 H, CH), 3.91 (m, 1 H,
13C NMR (DMSO-d6): d = 115.3, 122.7 (q, 1JCF = 275 Hz), 122.9 (q,
1JCF = 275 Hz), 127.7 (q, 2JCF = 35 Hz), 133.9, 141.4 (q, 2JCF = 35
Hz), 149.5, 161.4.
CH), 4.44 (m, 1 H, CH), 4.59–4.67 (m, 2 H, CH), 4.81 (br t, 3JHH
=
6.2 Hz, 1 H, CH), 4.95 (d, 3JHH = 6.4 Hz, 1 H), 7.71 (s, 1 H, CH),
8.11 (s, 1 H, CH).
MS (EI, 70 eV): m/z (%) = 255 [M+] (100), 254 (21).
13C NMR (DMSO-d6): d = 28.4, 45.7, 59.0, 63.9, 71.9, 74.0, 115.7,
122.6 (q, 1JCF = 275 Hz), 122.8 (q, 1JCF = 275 Hz), 127.9 (q, 2JCF
=
2-{[5,7-Bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-3-
yl]methoxy}propane-1,3-diyl Dibenzoate (35)
35 Hz), 133.7, 141.0 (q, 2JCF = 35 Hz), 149.0, 161.9.
Compound 35 was prepared according to a published procedure.14
MS (EI, 70 eV): m/z (%) = 385 [M+] (14), 368 (32), 367 (100), 332
(21), 311 (72), 299 (60), 271 (22), 254 (43), 202 (23), 169 (13), 131
(32),
Yellow oil; yield: 0.65 g (57%); Rf = 0.90 (EtOAc–hexane, 1:3).
1H NMR (DMSO-d6): d = 4.33 (m, 4 H, CH2), 4.81 (br m, 1 H, CH),
6.01 (br s, 2 H, CH2), 7.35 (br m, 6 H, CH), 7.77 (s, 1 H, CH), 7.87
(d, 3JHH = 7.2 Hz, 4 H), 8.37 (s, 1 H, CH).
{4-[5,7-Bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-3-yl]cy-
clopent-2-enyl}methanol (41)
Compound 41 was prepared according to a published procedure.16
13C NMR (DMSO-d6): d = 62.3, 69.7, 76.7, 115.4, 122.1 (q, 1JCF
=
1
275 Hz), 122.7 (q, JCF = 275 Hz), 127.5 (q, 2JCF = 35 Hz), 128.8,
Yellow oil; yield: 0.18 g (51%); Rf = 0.55 (EtOAc).
2
129.7, 130.5, 133.3, 133.9, 141.4 (q, JCF = 35 Hz), 149.1, 161.7,
1H NMR (DMSO-d6): d = 1.68 (ddd, 2JHH = 12.5, 3JHH = 5.3, 3JHH
=
188.9.
5.3 Hz, 2 H, CH), 2.60 (ddd, 2JHH = 13.2, 3JHH = 8.2, 3JHH = 8.2 Hz,
2 H, CH), 2.99 (br m, 1 H, CH), 3.41 (br s, 1 H, OH), 3.57 (d,
2JHH = 11.4 Hz, 2 H, OCH2), 5.37–5.44 (m, 1 H, CH), 5.90 (ddd,
MS (EI, 70 eV): m/z (%) = 567 [M+] (47), 445 (19), 313 (37), 283
(33), 282 (17), 161 (27), 105 (100), 77 (19), 67 (11).
2JHH = 5.5, 3JHH = 2.1, 3JHH = 2.1 Hz, 1 H, CH), 6.17 (ddd, 2JHH
=
13.2, 3JHH = 2.4, 3JHH = 2.4 Hz, 1 H, CH), 7.77 (s, 1 H, CH), 8.24 (s,
2-{[5,7-Bis(trifluoromethyl)-3H-imidazo[4,5-b]pyridin-3-
yl]methoxy}propane-1,3-diol (36)
1 H, CH).
To a solution of the acylated nucleoside 35 (1 mmol) in abs. MeOH
(5 mL) a sat. solution of NH3 in MeOH (20 mL) was added drop-
wise at 0 °C. The mixture was stirred for another 30 min and left
overnight at r.t. The solvent was removed under reduced pressure,
and the formed material was kept for the next 24 h on a vacuum line.
The resultant yellow material was purified by column chromatogra-
phy on silica gel.
13C NMR (DMSO-d6): d = 35.4, 47.0, 57.1, 64.3, 115.3, 122.7 (q,
1
2
1JCF = 275 Hz), 122.9 (q, JCF = 275 Hz), 127.7 (q, JCF = 35 Hz),
128.2, 133.9, 137.9, 141.4 (q, 2JCF = 35 Hz), 149.5, 161.4.
MS (EI, 70 eV): m/z (%) = 351 [M+] (27), 333 (100), 293 (14), 291
(11), 79 (36), 57 (38).
Yellow oil; yield: 0.27 g (74%); Rf = 0.75; (EtOAc–hexane, 1:1).
References
1H NMR (DMSO-d6): d = 4.27 (m, 4 H, CH2), 4.47 (br s, 2 H, OH),
4.54 (br m, 1 H, CH), 5.88 (br s, 2 H, CH2), 7.79 (s, 1 H, CH), 8.44
(s, 1 H, CH).
(1) (a) Dubey, P. K.; Kumar, R. V.; Naidu, A.; Kulkarni,
S. M. A. Asian J. Chem. 2002, 14, 1129. (b) Lee, S. Ch.;
Choi, J. S.; Oh, J. H.; Park, B.; Kim, Y. E.; Lee, J. H.; Shin,
D.; Kim, Ch. M.; Hyun, Y.-L.; Lee, C. h. S.; Cho, J.-M.; Ro,
S. WO 83978 2007; Chem. Abstr. 2007, 147, 817587.
(c) Kelly, M. G.; Kincaid, J.; Duncton, M.; Sahasrabudhe,
K.; Janagani, S.; Upasani, R. B.; Wu, G.; Fang, Y.; Wei,
Zh.-L. US 194801 2006; Chem. Abstr. 2006, 145, 889269.
(d) Randolph, J. T.; Chen, H.; Degoey, D. A.; Flentge,
Ch. A.; Flosi, W. J.; Grampovnik, D. J.; Huang, P. P.;
Hutchinson, D. K.; Kempf, D. J.; Klein, L. L.; Yeung, M. C.
US 159469 2005; Chem. Abstr. 2005, 143, 641882.
(e) Kivlighn, S. D.; Zingaro, G. J.; Gabel, R. A.; Broten,
T. P.; Schorn, T. W.; Schaffer, L. W.; Naylor, E. M.;
Chakravarty, P. K.; Patchett, A. A.; Greenlee, W. J.; Siegl,
P. K. S. Am. J. Hypertens. 1995, 8, 58.
(2) (a) Pagani, E. D.; Dundore, R. L.; Bode, D. C.; Bacon, E. R.;
Singh, B.; Lesher, G. Y.; Buchholz, R. A.; Silver, P. J. J.
Cardiovasc. Pharmacol. 1994, 24, 403. (b) Joseph, E. C.;
Rees, J. A.; Dayan, A. Toxicol. Pathol. 1996, 24, 436.
(c) Garvey, D. S.; Saenz de Tejada, I.; Earl, R. A.;
Khanapure, S. P. US 6331543, 2001; Chem. Abstr. 2001,
136, 916407.
13C NMR (DMSO-d6): d = 62.9, 71.0, 78.7, 115.3, 122.3 (q, 1JCF
=
1
275 Hz), 122.8 (q, JCF = 275 Hz), 128.1 (q, 2JCF = 35 Hz), 133.9,
141.3 (q, 2JCF = 35 Hz), 149.1, 161.5.
MS (EI, 70 eV): m/z (%) = 359 [M+] (13), 341 (17), 340 (100), 268
(31), 57 (59).
{(3aR,4R,6R,6aS)-6-[5,7-Bis(trifluoromethyl)-3H-imidazo[4,5-
b]pyridin-3-yl]-2,2-dimethyltetrahydro-3aH-cyclopen-
ta[d][1,3]dioxol-4-yl}methanol (38)
Compound 38 was prepared according to a published procedure.15
Yellow oil; yield: 0.48 g (57%); Rf = 0.60 (hexane–EtOAc, 3:1).
1H NMR (DMSO-d6): d = 1.25 (s, 3 H, CH), 1.53 (s, 3 H, CH), 2.43–
2.57 (br m, 3 H, CH), 3.72 (br m, 2 H, CH), 4.61 (dd, 3JHH = 6.0, 4.3
Hz, 1 H, CH), 4.85–4.91 (br m, 2 H, CH), 5.17 (dd, 3JHH = 6.8, 6.0
Hz, 1 H, CH), 7.71 (s, 1 H, CH), 8.13 (s, 1 H, CH).
13C NMR (DMSO-d6): d = 25.0, 27.7, 33.3, 45.0, 60.9, 61.5, 80.0,
1
1
83.4, 115.0, 116.3, 122.7 (q, JCF = 275 Hz), 122.8 (q, JCF = 275
Hz), 127.8 (q, 2JCF = 35 Hz), 133.9, 141.1 (q, 2JCF = 35 Hz), 149.9,
161.0.
(3) (a) Ida, K.; Otsubo, N.; Kuboyama, T.; Arai, H.; Watanabe,
A.; Saki, M.; Hiura, N.; Manabe, H.; Takada, H.; Saito, J.
WO 82905, 2005; Chem. Abstr. 2005, 143, 979654.
(b) Magnuson, S.; Dixon, J.; Phillips, B.; Khire, U.; Wang,
L.; Zhang, Z.; Patel, M.; Kumarasinghe, E. S.; Wickens, P.;
Oblague, A. WO 64932, 2007; Chem. Abstr. 2007, 147,
618350. (c) Bavetsias, V.; Sun, C.; Bouloc, N.; Reynisson,
J.; Workman, P.; Linardopoulos, S.; McDonald, E. Bioorg.
Med. Chem. Lett. 2007, 17, 6567.
MS (EI, 70 eV): m/z (%) = 425 [M+] (17), 410 (12), 392 (33), 307
(25), 255 (21), 247 (37), 209 (67), 169 (100), 155 (67).
(1R,2S,3R,5R)-3-[5,7-Bis(trifluoromethyl)-3H-imidazo[4,5-
b]pyridin-3-yl]-5-(hydroxymethyl)cyclopentane-1,2-diol (39)
Compound 39 was obtained from 38 according to a published pro-
cedure.9g
Synthesis 2009, No. 11, 1865–1875 © Thieme Stuttgart · New York